deltaBaff a novel isoform of the TNF family protein BAFF

描述（由申请人提供）：这是一项RO3申请，旨在研究由申请人发现并表征的新蛋白，称为deltaBAFF。DeltaBAFF是B细胞调节因子BAFF的一种新型剪接异构体，BAFF是一种具有强大免疫调节作用的TNF家族蛋白。BAFF的过表达导致过量的B细胞积累、活化、自身抗体和狼疮样疾病，而缺乏δ BAFF导致外周B细胞免疫缺陷。了解BAFF介导的B细胞存活和自身免疫之间的平衡是很重要的。将测试deltaBAFF在抑制BAFF的作用和调节B淋巴细胞稳态中起作用的想法。将测试通过转基因在体内特异性改变δ BAFF与全长BAFF表达的比率的效果。将测试同多聚体或异多聚体对膜表达和生物学功能的影响。这些研究的长期目标是了解B淋巴细胞的稳态。了解δ BAFF的功能可能为我们了解和治疗自身免疫性疾病和B淋巴癌提供线索。

DESCRIPTION (provided by applicant): This is an RO3 application to investigate a new protein discovered and characterized by the applicant, called deltaBAFF. DeltaBAFF is a novel splicing isoform of the B cell regulator BAFF, a TNF-family protein with powerful immunoregulatory effects. Over-expression of BAFF leads to excessive B cell accumulation, activation, autoantibodies, and lupus-like disease, whereas an absence of deltaBAFF causes peripheral B cell immunodeficiency. It is important to understand how the balance between BAFF-mediated B cell survival and autoimmunity is controlled. The idea that deltaBAFF plays a role in restraining the effects of BAFF and regulating B lymphocyte homeostasis will be tested. The effects of specifically altering the ratio of deltaBAFF to full-length BAFF expression in vivo by transgenesis will be tested. The effects of homomultimers or heteromultimers on membrane expression and biological function will be tested. The long-term goal of these studies is to understand B lymphocyte homeostasis. Understanding the function of deltaBAFF may provide clues to help us understand and cure autoimmune disease and B lymphoid cancer.